title: Mapping corpus callosum morphology in twin pairs discordant for bipolar disorder.
abstract: Callosal volume reduction has been observed in patients with bipolar disorder, but whether these deficits reflect genetic vulnerability to the illness remains unresolved. Here, we used computational methods to map corpus callosum abnormalities in a population-based sample of twin pairs discordant for bipolar disorder. Twenty-one probands with bipolar I disorder (mean age 44.4 ± 7.5 years; 48% female), 19 of their non-bipolar co-twins, and 34 demographically matched control twin individuals underwent magnetic resonance imaging. Three-dimensional callosal surface models were created to visualize its morphologic variability and to localize group differences. Neurocognitive correlates of callosal area differences were additionally investigated in a subsample of study participants. Bipolar (BPI) probands, but not their co-twins, showed significant callosal thinning and area reduction, most pronounced in the genu and splenium, relative to healthy twins. Altered callosal curvature was additionally observed in BPI probands. In bipolar probands and co-twins, genu and splenium midsagittal areas were significantly correlated with verbal processing speed and response inhibition. These findings suggest that aberrant connections between cortical regions--possibly reflecting decreased myelination of white matter tracts--may be involved in bipolar pathophysiology. However, findings of callosal thinning appear to be disease related, rather than reflecting genetic vulnerability to bipolar illness.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA. cbearden@mednet.ucla.edu
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Bearden
authors.forename: Theo G M
authors.initials: TG
authors.lastname: van Erp
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Dutton
authors.forename: Christina
authors.initials: C
authors.lastname: Boyle
authors.forename: Sarah
authors.initials: S
authors.lastname: Madsen
authors.forename: Eileen
authors.initials: E
authors.lastname: Luders
authors.forename: Tuula
authors.initials: T
authors.lastname: Kieseppa
authors.forename: Annamari
authors.initials: A
authors.lastname: Tuulio-Henriksson
authors.forename: Matti
authors.initials: M
authors.lastname: Huttunen
authors.forename: Timo
authors.initials: T
authors.lastname: Partonen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Jouko
authors.initials: J
authors.lastname: Lönnqvist
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.forename: Tyrone D
authors.initials: TD
authors.lastname: Cannon
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D001931:Brain Mapping / Q000379:methods*; D015331:Cohort Studies; D003337:Corpus Callosum / Q000473:pathology*; D004200:Diseases in Twins / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012042:Registries